An Iron-Scavenging and Hydrogen-Releasing Microneedle Patch Suppresses Ferroptosis and Promotes Spinal Cord Repair

Spinal cord injury (SCI) is a devastating trauma to the central nervous system, causing permanent functional nerve defects. A key therapeutic challenge is the inhibition of the secondary injury cascade, specifically the progressive neural damage from iron overload-induced ferroptosis and oxidative stress. To target these dual mechanisms, we developed a dual-functional, iron-scavenging, and hydrogen-releasing microneedle patch (MN/MON@AB) composed of ammonia borane (AB)-loaded, amino-functionalized mesoporous organosilica nanoparticles (MON-NH2) embedded in a biodegradable silk fibroin array. This system functions via a dual-target mechanism: amino groups chelate excess iron ions to suppress the Fenton reaction, while AB provides sustained release of molecular hydrogen (H2) in the acidic injury microenvironment to neutralize reactive oxygen species (ROS). MN/MON@AB has been found to reduce the intracellular Fe2+ levels by 46.7%, nearly doubling the expression of the key ferroptosis regulator GPX4, and largely alleviating lipid peroxidation in vitro. In a murine SCI model, the patch significantly reduced spinal iron deposition (p < 0.0001) and promoted marked locomotor recovery (p < 0.001). Featuring combined localized iron chelation and sustained antioxidant delivery, the present strategy offers a broadly applicable and pioneering therapeutic platform for treating acute neural injuries and subsequent neurodegenerative processes.